Actin mutations in dilated cardiomyopathy, a heritable form of heart failure
Actin mutations in dilated cardiomyopathy, a heritable form of heart failure
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DOI：
10.1126/science.280.5364.750
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发表时间：
1998-05-01
期刊：
影响因子：
56.9
通讯作者：
Keating, MT
中科院分区：
文献类型：
--
作者：
Olson, TM;Michels, VV;Keating, MT
为了验证肌动蛋白功能障碍导致心力衰竭的假设，对遗传性特发性扩张型心肌病(IDC)患者进行了心脏肌动蛋白基因(ACTC)突变检测。在两个不相关的家系中发现了与IDC共分离的ACTC错义突变。这两个突变都会影响附着在Z带和插入盘上的肌动蛋白结构域中普遍保守的氨基酸。再加上之前的数据显示，dystrophin突变也会导致扩张型心肌病，这些结果增加了这样一种可能性，即心肌细胞内力传递缺陷是导致心力衰竭的机制之一。
To test the hypothesis that actin dysfunction leads to heart failure, patients with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for mutations in the cardiac actin gene (ACTC). Missense mutations in ACTC that cosegregate with IDC were identified in two unrelated families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Coupled with previous data showing that dystrophin mutations also cause dilated cardiomyopathy, these results raise the possibility that defective transmission of force in cardiac myocytes is a mechanism underlying heart failure.